Anti-CD47 monoclonal antibody and use thereof

Abstract

An anti-CD47 monoclonal antibody and use thereof. The provided anti-CD47 monoclonal antibody can effectively inhibit tumor growth. Blocking human SIRP and human CD47 signals may enhance macrophage phagocytosis of tumor cells, prevent the tumor cells from escaping a tumor immune defense system, and have an anti-tumor function. Blocking association between the CD47 on a tumor cell surface and the SIRP on a macrophage surface may block a “do not eat me” signal from the tumor cells, promoting tumor cell recognition and uptake of macrophages, and thereby facilitating tumor cells to be phagocytosed. The association between the CD47 on a tumor cell surface and the SIRP on a macrophage surface is a common “do not eat me” signal. The anti-CD47 antibody, as a very promising target in the tumor immune system, will play a powerful and effective role in human cancer therapy.

What is claimed is: 
     
       1. An anti-CD47 monoclonal antibody, characterized in that, the antibody comprises a heavy chain variable region and a light chain variable region, wherein:
 (I) the amino acid sequence of the heavy chain variable region is represented by SEQ ID NO: 1 or SEQ ID NO: 2 or SEQ ID NO: 3 or SEQ ID NO: 4 or SEQ ID NO: 5 or SEQ ID NO: 6 or SEQ ID NO: 7; and 
 (II) the amino acid sequence of the light chain variable region is represented by SEQ ID NO: 8 or SEQ ID NO: 9 or SEQ ID NO: 10 or SEQ ID NO: 11 or SEQ ID NO: 12 or SEQ ID NO: 13 or SEQ ID NO: 14. 
 
     
     
       2. The anti-CD47 monoclonal antibody according to  claim 1 , wherein:
 (i) the heavy chain variable region with the amino acid sequence is represented by SEQ ID NO: 4, and 
 (ii) the light chain variable region with the amino acid sequence is represented by SEQ ID NO: 11. 
 
     
     
       3. The anti-CD47 monoclonal antibody according to  claim 1 , characterized in that,
 the hypervariable regions of the heavy chain variable region are HVR-H1 HVR-H2, and HVR-H3; 
 in SEQ ID NO: 2, the hypervariable region HVR-H1 sequence is represented by SEQ ID NO: 45; the HVR-H2 sequence is represented by SEQ ID NO: 46; and the HVR-H3 sequence is represented by SEQ ID NO: 47; 
 in SEQ ID NO: 5, the hypervariable region HVR-H1 sequence is represented by SEQ ID NO: 48; the HVR-H2 sequence is represented by SEQ ID NO: 49; and the HVR-H3 sequence is represented by SEQ ID NO: 50; and 
 in SEQ ID NO: 6, the hypervariable region HVR-H1 sequence is represented by SEQ ID NO: 51; the HVR-H2 sequence is represented by SEQ ID NO: 52; and the HVR-H3 sequence is represented by SEQ ID NO: 53; 
 the hypervariable regions of the light chain variable region are HVR-L1, HVR-L2, and HVR-L3; 
 SEQ ID NO: 9, the hypervariable region HVR-L1 sequence is represented by SEQ ID NO: 54; the HVR-L2 sequence is represented by SEQ ID NO: 55; and the HVR-L3 sequence is represented by SEQ ID NO: 56; 
 in SEQ ID NO: 12, the hypervariable region HVR-L1 sequence is represented by SEQ ID NO: 57; the HVR-L2 sequence is represented by SEQ ID NO: 58; and the HVR-L3 sequence is represented by SEQ ID NO: 59; and 
 in SEQ ID NO: 13, the hypervariable region HVR-L1 sequence is represented by SEQ ID NO: 60; the HVR-L2 sequence is represented by SEQ ID NO: 61; and the HVR-L3 sequence is represented by SEQ ID NO: 62. 
 
     
     
       4. The anti-CD47 monoclonal antibody according to  claim 1 ,
 wherein: 
 (i) the heavy chain variable region is represented by SEQ ID NO: 5, and 
 (ii) the light chain variable region is represented by SEQ ID NO: 12. 
 
     
     
       5. A medicament, characterized in that, it comprises the anti-CD47 monoclonal antibody according to  claim 1 . 
     
     
       6. The anti-CD47 monoclonal antibody according to  claim 1 , wherein:
 (i) the heavy chain variable region is represented by SEQ ID NO: 2, and 
 (ii) the light chain variable region is represented by SEQ ID NO: 9. 
 
     
     
       7. The anti-CD47 monoclonal antibody according to  claim 6 , characterized in that, the heavy chain type is IgG1, IgG3 or IgM; and the light chain type is κ. 
     
     
       8. A hybridoma cell strain, which produces the anti-CD47 monoclonal antibody according to  claim 6 . 
     
     
       9. The anti-CD47 monoclonal antibody according to  claim 1 , wherein:
 (i) the amino acid sequence of the heavy chain variable region is represented by SEQ ID NO: 6, and 
 (ii) the amino acid sequence of the light chain variable region is represented by SEQ ID NO: 13. 
 
     
     
       10. The anti-CD47 monoclonal antibody according to  claim 9 , characterized in that, the heavy chain type is IgG1, IgG3 or IgM; and the light chain type is κ. 
     
     
       11. A hybridoma cell strain, which produces the anti-CD47 monoclonal antibody according to  claim 9 .